Obesity is prevalent,is associated with many health hazards, and its treatment replete with frustration. In addition, the contribution of alterations in metabolic rate to the development of obesity or its recurrence are unknown. The current studies will use a doubly-labeled water technique to measure ambulatory, free living metabolic rate in obese subjects before and after weight reduction and compare the reduced obese subjects to normal lean controls. Our goal is to determine if the reduced obese are at a metabolic disadvantage which would lead to weight gain at normal calorie intake. Protein metabolism (leucine and lysine flux) will be evaluated before and after weight reduction and in normal controls to determine if abnormal protein metabolism normalizes with weight reduction and to determine if the decrease in resting metabolic rate after weight reduction is related to reduced protein turnover. Both resting and 24 h metabolic rate will be expressed as a function of lean body mass as determined by 40K counting and total body water. Obesity will also be classified by anthropomorphic measurements as well as MRI. The obesity type can then be examined for its effects on insulin sensitivity, protein metabolism,loss of lean body mass with weight reduction, and whether body type affects metabolic rate at reduced weight. These studies will allow us to better understand the pathophysiology of obesity and perhaps allow us to design more rational therapeutic regimens to enhance our long term success at treating obesity.